SCN5A Variant V856L

Summary of observed carriers, functional annotations, and structural context for SCN5A V856L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

7%

0/11 effective observations

Estimated BrS1 penetrance

12%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

V856L is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 0 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-2.97 0.951 3.44 0.895 15 5

PROVEAN scores below -2 suggest deleterious impact. REVEL scores above 0.5–0.75 are often interpreted as likely pathogenic. PolyPhen-2 scores above 0.85 are typically pathogenic. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).

Reported carrier data

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT3 BrS1 Other Other Disease
Literature, cohort, and gnomAD – 1 1 0 0 –
Variant features alone – 15 14 0 1 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

Nearby variants

Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.

Previously observed variants near V856L.
Neighbour residue Distance (Å) Observed variants
891 10 I891N, I891T,
880 14
888 12
848 13 I848F,
223 7 V223L,
856 0 V856L, V856L,
890 12 I890T,
919 11
862 10
859 6
894 14 I894M,
149 13
863 13
925 13 I925F,
227 12 L227P,
887 9
864 13
886 14 H886Q, H886Q, H886P,
216 11 S216L, S216X,
851 9 c.2552_2553dupGT, F851L, F851L, p.F851CfsX19, F851L, c.2550_2551dupGT,
221 7
196 15
852 6
854 6 c.2559delT,
222 10 R222X, R222L, R222Q,
224 9 L224F,
857 4 G857D,
902 14
882 13
881 9
849 11
226 12 A226V, A226G,
921 11
922 11 V922I,
860 6 p.L860fsx89,
920 14
889 15
858 7 M858L, M858L,
144 14
217 10
918 8
855 5
917 13 L917V, L917R,
865 14
913 14
916 15
148 10
884 11
906 13
910 14 S910L,
885 15
847 14
203 13
152 14 D152N,
853 6
219 10 R219H, p.R219HfsX11, R219C, c.656_657insATTCA,
225 14 R225W, R225Q,
151 13
218 12
883 13
915 11 C915R,
215 14 p.L215CfsX10,
850 10 c.2549_2550insTG, V850M
914 10
200 13
145 13
861 8 c.2582_2583delTT, p.F861WfsX90,
220 5 T220I,